Nanoemulsion respiratory syncytial virus (RSV) subunit vaccine
Inventors
Fattom, Ali I. • Hamouda, Tarek • Bitko, Vira • Baker, Jr., James R.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9561271-B2
Publication Date
2017-02-07
Expiration Date
Abstract
The present application relates to the field of immunology, in particular, a vaccine composition of respiratory syncytial virus (RSV) surface proteins, Fusion (F) and Glycoprotein (G) proteins subunit vaccine preferentially mixed with the immune cell targeting and enhancer, nanoemulsion to induce a protective immune response and avoid vaccine-induce disease enhancement.
Core Innovation
The invention relates to a vaccine composition comprising at least one isolated respiratory syncytial virus (RSV) antigen or an antigenic fragment thereof and an immune-enhancing oil-in-water nanoemulsion or a dilution thereof. The nanoemulsion comprises droplets having an average size of about 1000 nm or less, and includes an aqueous phase, at least one oil, at least one surfactant, and at least one organic solvent. The at least one RSV antigen is comprised within the nanoemulsion.
The disclosed compositions and methods are directed to inducing protective immunity against diseases caused by respiratory syncytial viruses while avoiding vaccine-enhanced disease. The formulation is characterized as preferentially incorporating RSV surface immunogens into the immune-enhancing nanoemulsion adjuvant, including RSV F and/or RSV G proteins and/or antigenic fragments. Where stated, RSV virion particles may be optionally inactivated and incorporated as part of the RSV components within the vaccine formulation.
The invention further describes protective immunity and cross-protection between RSV strains, including RSV strain L19 and RSV strain A2. Preclinical findings described include improved viral clearance after live RSV challenge, with reduced airway hyperreactivity, mucus hypersecretion, and inflammatory readouts, together with antigen-specific antibody responses and cytokine profiles consistent with Th1/Th2/Th17 skewing.
Claims Coverage
Two independent claims are identified. Across these independent claims, the inventive features center on an immune-enhancing oil-in-water nanoemulsion with droplets of average size about 1000 nm or less, and an isolated RSV antigen or antigenic fragment comprised within the nanoemulsion, together with enhanced immune response and enhanced immunity against RSV diseases.
RSV antigen in defined immune-enhancing nanoemulsion
A vaccine composition comprising at least one isolated RSV antigen or an antigenic fragment thereof and an immune-enhancing nanoemulsion or a dilution thereof, comprising droplets having an average size of about 1000 nm or less, wherein the at least one RSV antigen is comprised within the nanoemulsion.
Nanoemulsion structure with aqueous phase, oil, surfactant, and organic solvent
The immune-enhancing nanoemulsion includes an aqueous phase, at least one oil, at least one surfactant, and at least one organic solvent, with droplets having an average size of about 1000 nm or less.
Greater immune response with nanoemulsion-formulated RSV antigen
Administration of the vaccine composition results in a greater immune response as compared to administration of the at least one isolated antigen or antigenic fragment thereof in the absence of the nanoemulsion.
Method of inducing enhanced immunity against RSV diseases by nanoemulsion-formulated RSV antigen
A method for inducing an enhanced immunity against diseases caused by respiratory syncytial viruses comprising administering to a subject an effective amount of vaccine comprising at least one isolated RSV antigen or an antigenic fragment thereof and an immune-enhancing nanoemulsion or a dilution thereof, comprising droplets having an average size of about 1000 nm or less, wherein the isolated RSV antigen is comprised within the nanoemulsion.
The independent claims center on an immune-enhancing oil-in-water nanoemulsion with droplets of average size about 1000 nm or less, where an isolated RSV antigen or antigenic fragment is comprised within the nanoemulsion. The vaccine composition is claimed to produce a greater immune response than the isolated antigen without the nanoemulsion, and the method claim recites inducing enhanced immunity by administering the defined vaccine effective amount.
Stated Advantages
Protective immunity against diseases caused by respiratory syncytial viruses while avoiding vaccine-enhanced disease.
Induction of Th1 immune response, Th2 immune response, and Th17 immune response, including IL-17.
Reduced airway hyperreactivity and inflammation.
Improved viral clearance after live RSV challenge.
Cross-protection between RSV strains, including L19 and A2.
Documented Applications
Use of the vaccine composition to induce enhanced immunity against diseases caused by respiratory syncytial viruses.
Preclinical evaluation in mice and cotton rats, including cytokine profiles, antibody responses, airway hyperreactivity, inflammation, viral transcript/protein clearance, and histology after live RSV challenge.
Formulation and administration contexts described include intranasal and intramuscular administration, and application to subject populations including infants, elderly subjects, subjects with chronic obstructive pulmonary disease, and transplant patients.
Interested in licensing this patent?